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The protein corona suppresses the cytotoxic and pro-inflammatory response in lung epithelial cells and macrophages upon exposure to nanosilica

  • Nanotoxicology
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Abstract

Engineered amorphous silica nanoparticles (nanosilica) are one of the most abundant nanomaterials and are widely used in industry. Furthermore, novel nanosilica materials are promising theranostic tools for biomedicine. However, hazardous effects of nanosilica especially after inhalation into the lung have been documented. Therefore, the safe development of nanosilica materials urgently requires predictive assays to monitor toxicity. Here, we further investigate the impact of the protein corona on the biological activity of two different types of nanosilica (colloidal and pyrogenic) in lung cells. As previously described, adsorption of serum proteins to the nanosilica surface suppresses cytotoxicity in macrophages and lung epithelial cells. As the increase of pro-inflammatory mediators is a hallmark of inflammation in the lung upon nanosilica exposure, we studied the potential coupling of the cytotoxic and pro-inflammatory response in A549 human lung epithelial cells and RAW264.7 mouse macrophages. Indeed, cytotoxicity precedes the onset of pro-inflammatory gene expression and cytokine release as exemplified for IL-8 in A549 cells and TNF-alpha in RAW264.7 macrophages after exposure to 0–100 µg/mL nanosilica in medium without serum. Formation of a protein corona not only inhibited cellular toxicity, but also the pro-inflammatory response. Of note, uptake of nanosilica into cells was negligible in the absence, but enhanced in the presence of a protein corona. Hence, the prevailing explanation that the protein corona simply interferes with cellular uptake thus preventing adverse effects needs to be revisited. In conclusion, for the reliable prediction of adverse effects of nanosilica in the lung, in vitro assays should be performed in media not complemented with complete serum. However, in case of different exposure routes, e.g., injection into the blood stream as intended for biomedicine, the protein corona prevents acute toxic actions of nanosilica.

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Acknowledgements

RL and AMW were funded by a grant of the Federal Institute for Risk Assessment (BfR), Germany (BfR-ZEBET-1329-475) which is greatly acknowledged.

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Authors and Affiliations

  1. Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von- Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany

    Regina Leibe, I-Lun Hsiao, Susanne Fritsch-Decker, Ulrike Kielmeier, Ane Marit Wagbo, Benjamin Voss, Annemarie Schmidt, Sarah Dorothea Hessman, Silvia Diabaté & Carsten Weiss

  2. School of Food Safety, College of Nutrition, Taipei Medical University, 250 Wuxing St., Taipei, 11031, Taiwan

    I-Lun Hsiao

  3. Department of Biosciences, Allergy Cancer BioNano Research Centre (ACBN), University of Salzburg, Hellbrunnerstraße 34, 5020, Salzburg, Austria

    Albert Duschl

  4. Biomedical Sciences, Salzburg University of Applied Sciences, Urstein Süd 1, 4512, Puch bei Hallein, Austria

    Gertie Janneke Oostingh

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  1. Regina Leibe
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  2. I-Lun Hsiao
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Correspondence to Silvia Diabaté or Carsten Weiss.

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Leibe, R., Hsiao, IL., Fritsch-Decker, S. et al. The protein corona suppresses the cytotoxic and pro-inflammatory response in lung epithelial cells and macrophages upon exposure to nanosilica. Arch Toxicol 93, 871–885 (2019). https://doi.org/10.1007/s00204-019-02422-9

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